Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection.
Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27(+) HIV seronegative vaccinee persistent HIV-specific vaccine-induced anti-Gag CD4(+) and CD8(+) T cell responses. Although these responses exhibited those characteristics (multifunctionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8(+) T cells expanded, but both CD4(+) and CD8(+) T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection.
Betts, MR; Exley, B; Price, DA; Bansal, A; Camacho, ZT; Teaberry, V; West, SM; Ambrozak, DR; Tomaras, G; Roederer, M; Kilby, JM; Tartaglia, J; Belshe, R; Gao, F; Douek, DC; Weinhold, KJ; Koup, RA; Goepfert, P; Ferrari, G
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